TIMOTHY ROEHRS, PH.D.,
is director of research at the Sleep Disorders and Research Center of
the Henry Ford Hospital and adjunct professor of psychiatry in the Department
of Psychiatry and Behavioral Neuroscience, Wayne State University, Detroit,
Michigan.

THOMAS ROTH, PH.D., is division head
of the Sleep Disorders and Research Center of the Henry Ford Hospital
and adjunct professor of psychiatry in the Department of Psychiatry
and Behavioral Neuroscience, Wayne State University, Detroit, Michigan.

This work has been supported by National
Institute on Alcohol Abuse and Alcoholism grant R01-AA-11264.

The
study of alcohols effects on sleep dates back to the late 1930s. Since
then, an extensive literature has described alcohols effects on the
sleep of healthy, nonalcoholic people. For example, studies found that in
nonalcoholics who occasionally use alcohol, both high and low doses of alcohol
initially improve sleep, although high alcohol doses can result in sleep disturbances
during the second half of the nocturnal sleep period. Furthermore, people
can rapidly develop tolerance to the sedative effects of alcohol. Researchers
have investigated the interactive effects of alcohol with other determinants
of daytime sleepiness. Such studies indicate that alcohol interacts with sleep
deprivation and sleep restriction to exacerbate daytime sleepiness and alcohol-induced
performance impairments. Alcohols effects on other physiological functions
during sleep have yet to be documented thoroughly and unequivocally.

Alcohol
affects sleep, daytime alertness, and certain physiological processes that
occur during sleep. Its impact on human sleep has received much scientific
study dating back to early experiments by Kleitman (1939), described in his
book Sleep and Wakefulness.
In that monograph, the author summarizes the effects that alcohol consumed
60 minutes before bedtime has on body temperature and motility during sleep
in healthy nonalcoholic people. In the 1960s and 1970s, after scientists had
identified various sleep states (e.g., rapid eye movement [REM] sleep) and
had standardized electrophysiological methods to document sleep, research
on alcohols effects on the sleep of healthy nonalcoholic and noninsomniac
volunteers and on the sleep of alcoholics increased substantially. More recently,
with the emergence of the field of sleep-disorders medicine, researchers and
clinicians have focused their attention on alcohols effect on primary
sleep disorders, such as sleep apneas, which are short (i.e., 10 to 30 seconds
long) episodes of breathing obstruction. This attention to sleep disorders
also has sensitized investigators and clinicians to the impact that disrupted
and shortened sleep has on daytime alertness. As a result, various studies
have investigated the potential interactive effects of alcohol with daytime
alertness and daytime functioning in both healthy people and patients with
sleep disorders.

This article
provides an overview of alcohols effects on normal sleep, sleep physiology,
and daytime alertness in nonalcoholic people. (The accompanying article by
Brower, pp. 110-125 in this issue, discusses alcohols effects on sleep
in alcoholics.) The current article reviews normal sleep physiology, describes
alcohols effects on the various sleep states and sleep stages, and explores
some of the mechanisms through which alcohol may exert those effects. It then
summarizes the relationship of nocturnal sleep to daytime alertness and how
alcohol affects this relationship. The article ends with a discussion of alcohols
effects on sleep in people with primary insomnia.

Normal
Sleep Physiology

As
most people know from their own experience, sleep is not uniform through-out
the night. For example, at certain times during the night, it is very difficult
to wake a sleeping person, whereas at other times, the slightest sound will
alert the sleeper. Extensive studies have identified two different sleep states:
REM sleep and nonrapid eye movement (NREM) sleep. Furthermore, NREM sleep
can be divided into four stages based on how easy it is to arouse a sleeper
(i.e., how deep the sleep is).

These
different sleep states and sleep stages are defined based on scoring criteria
for three electrophysiological measurements that were first published in 1968
and have been employed ever since in sleep laboratories around the world.
The three electrophysiological measurements are recorded simultaneously and
comprise the following:

The
electroencephalogram (EEG), which traces the electrical activity of the
brain through electrodes placed on the scalp. These measurements produce
characteristic brain waves called alpha, beta, delta, and theta rhythms,
which differ in their frequencies.

The
electrooculogram (EOG), which measures eye movements through electrodes
placed on the skin around the eyes and records tiny electric signals that
occur when the eyes move.

The
electromyogram (EMG), which measures the electrical activity of muscles
through electrodes placed on the skin in various body regions. This technique
can measure even small muscle movement during sleep, such as twitching.

The following
paragraphs describe how these measurements are used to distinguish different
sleep states and sleep stages.

Stages
of NREM and REM Sleep

When comparing
the EEG readings of various sleep stages, researchers and clinicians assess
the frequency of the brain waves, measured in hertz (Hz), and the size, or
amplitude, of the brain waves, measured in microvolts. Both the frequency
and amplitude of the brain waves, as well as the EOG and EMG readings, differ
for various stages of wakefulness and sleep (see figure).

Samples of electrophysiological measurements of various sleep
stages. The four panels represent the measurements obtained during (A)
wakefulness; (B) stage 2 nonrapid eye movement (NREM) sleep (i.e., light
sleep); (C) stages 3 to 4 NREM sleep (deep or slow-wave sleep); and
(D) rapid eye movement (REM) sleep, which is associated with dreaming.
For each panel, the graphs labeled LOC and ROC represent measurements
of the left and right eye movements, respectively. The graph labeled
chin represents a measurement of small body movements, such
as of the chin muscles. The graphs labeled C3-A2 and O2A1 represent
two electroencephalogram (EEG) readings measuring brain activity in
certain brain regions. Finally, the electrocardiogram (EKG) measures
the heart rate. Each sleep stage is characterized by a specific pattern
of those readings. For example, during REM sleep the eyes move rapidly
compared with stage 2 NREM sleep. At the same time, the EEG readings
during REM sleep exhibit a higher frequency (i.e., number of waves per
second) and a lower amplitude (i.e., height of the peaks and valleys
of the waves) compared with stage 2 NREM sleep.

During
active wakefulness (i.e., when the person is awake and pursuing normal activities),
the EEG is characterized by high frequencies (i.e., 16 to 25 Hz) and low voltage
(i.e., 10 to 30 microvolts). EOG readings during wakefulness exhibit REMs,
and EMG readings generally show a high amplitude indicative of large muscle
movements.

During
relaxed wakefulness (i.e., when a person is awake but has his or her eyes
closed and is relaxed), the EEG is characterized by a pattern of alpha waves
with a frequency of 8 to 12 Hz and an amplitude of 20 to 40 microvolts. EOG
readings show slow, rolling movements at the transition to NREM sleep. EMG
readings show reduced amplitudes.

During
NREM sleep, the frequency of the brain waves slows further, whereas the amplitude
continues to increase. Thus, when the arousal threshold is highest (i.e.,
sleep is deepest), the EEG shows slow-wave sleep with a frequency
of 0.5 to 2.0 Hz and an amplitude of 75 microvolts or greater. EOG tracings
indicate cessation of eye movements, and EMG readings are gradually reduced,
even though episodic repositioning of the body and other motor events occur.
Based on the simultaneous analysis of all three measurements, NREM sleep is
classified into four stages that are characterized by increasing arousal thresholds.
Thus, stage 1 (i.e., drowsy sleep) has the lowest arousal threshold; stage
2 (i.e., light sleep) is intermediate; and stages 3 and 4 (i.e., deep sleep),
which collectively are also called slow-wave sleep (SWS), have the highest
arousal threshold.

During
REM sleep, cortical EEG readings revert to the low-voltage-mixed-frequency
pattern seen during drowsy sleep. The EOG displays the bursts of rapid eye
movements that give this stage its name. The EMG is reduced to its lowest
level for the night. In fact, most major voluntary muscle groups are paralyzed,
because certain nerve cells in the spinal cord (i.e., motor neurons) are not
responding to nerve signals. Arousal thresholds in REM are relatively low,
similar to NREM stages 1 or 2.

Tonic
and Phasic Periods of REM Sleep

REM sleep
can be further subdivided into tonic and phasic periods. During the tonic
periods, which account for the majority of REM sleep, muscle tone is decreased
and the EEG is similar to that seen during stage 1 NREM sleep. These tonic
periods are interrupted by intermittent phasic REM events. For example, the
eye movements characteristic of REM sleep occur in bursts during these phasic
periods, which are followed by the tonic periods of EOG quiescence. Coupled
with the bursts of eye movements are phasic muscle twitches, typically involving
peripheral muscles, although the reduced muscle tone (i.e., atonia) characteristic
of the tonic periods continues in most muscle groups. In addition, bursts
of activity occur during the phasic periods in body functions that are controlled
by the autonomic nervous system1 (1The autonomic nervous system
controls involuntary vital functions, such as the activities of the heart,
lungs, gastrointestinal tract, and glands.) ; these bursts
of activity are reflected by irregularities in cardiopulmonary function (e.g.,
heart rate and breathing rate).

NREMREM
Cycles

An ultradian
process--a biorhythm with a cycle of less than 24 hours-- within sleep controls
the alternation between NREM and REM sleep throughout the night. This ultradian
process creates cycles of NREM sleep followed by REM sleep that last approximately
90 to 120 minutes, yielding four to five such cycles over a standard 8-hour
sleep period. In the first two of those cycles, slow-wave NREM sleep predominates,
whereas the REM periods are generally quite short (i.e., 5 to 10 minutes).
Conversely, in the last two or three cycles, REM sleep predominates, sometimes
continuing uninterrupted for 30 to 40 minutes, and slow-wave NREM sleep is
almost nonexistent. (The significance of this ultradian cycling of NREM and
REM sleep to alcohols effects on sleep is described in the following
section of this article.)

Alcohols
Effects on Sleep Physiology

To
assess alcohols effects on sleep, investigators conducting a typical
sleep study administer alcohol to their subjects approximately 30 to 60 minutes
before bedtime. As a result of this schedule, alcohol concentrations in the
breath or blood usually peak at lights-out. Using this approach,
researchers have extensively studied alcohols effects in healthy people
at doses ranging from 0.16 to 1.0 grams of alcohol per kilogram of body weight
(g/kg) (Williams and Salamy 1972). These doses, which correspond to approximately
one to six standard drinks,2 (2A standard drink is defined
as one 12-ounce bottle of beer or wine cooler, one 5-ounce glass of wine,
and 1.5 ounces of 80 proof distilled spirits. ) yield breath
alcohol concentrations (BrACs) as high as 0.105 percent.3 (

3Breath alcohol concentrations
are another way of quantifying alcohol levels in the body and are approximately
the same as blood alcohol concentrations after a given alcohol dose.)
Some studies using this range of alcohol doses reported that the study
participants fell asleep faster (i.e., had reduced sleep latency) than without
alcohol consumption. One study found an increased sleep time at a low alcohol
dose (i.e., 0.16 g/kg) but detected no such effect at higher alcohol doses
(i.e., 0.32 and 0.64 g/kg) (Stone 1980).

Some investigators
have separately analyzed alcohols effects during the first and second
half of the nighttime sleep period. These studies found that particularly
at higher alcohol doses, increased wake periods or light stage 1 sleep periods
occurred during the second half of the sleep period (Williams et al. 1983;
Roehrs et al. 1991). This second-half disruption of sleep continuity is generally
interpreted as a rebound effect once alcohol has been completely
metabolized and eliminated from the body. The term rebound effect
means that certain physiological variables (e.g., sleep variables, such as
the amount of REM sleep) change in the opposite direction to the changes induced
by alcohol and even exceed normal levels once alcohol is eliminated from the
body. This effect results from the bodys adjustment to the presence
of alcohol during the first half of the sleep period in an effort to maintain
a normal sleep pattern. Once alcohol is eliminated from the body, however,
these adjustments result in sleep disruption. This hypothesis is supported
by the known rate of alcohol metabolism, which leads to a decrease in BrAC
of 0.01 to 0.02 per-cent per hour. Given that in such experiments, the typical
peak BrACs measured shortly before sleep are 0.06 to 0.08 percent, alcohol
metabolism at this rate would be completed within 4 to 5 hours of sleep onset;
thus, the sleep disruption during the second half of the night would coincide
with the clearance of alcohol from the body.

In addition
to these effects on sleep initiation and sleep maintenance, researchers have
found that alcohol consistently affects the proportions of the various sleep
stages. Thus, most studies have reported a dose-dependent suppression of REM
sleep at least during the first half of the sleep period (Williams and Salamy
1972). As noted earlier, the amount of REM sleep time is lower during the
first half of the night relative to the second half of the night; consequently,
the full REM-suppressive effect of alcohol is probably underestimated in most
studies. To determine alcohols full effect on REM sleep, investigators
would need to administer an additional alcohol dose in the middle of the night,
thereby causing alcohols peak concentrations to coincide with the majority
of REM sleep time. No such studies have been conducted, however.

Those
studies that have demonstrated alcohol-induced REM suppression during the
first half of the sleep period also have frequently found an REM rebound (i.e.,
longer-than-normal REM periods) during the second half of the night (Williams
and Salamy 1972). As a result, the overall amount of REM sleep in subjects
receiving alcohol before sleeping did not differ from that in subjects receiving
a nonalcoholic drink (i.e., a placebo). As with the increased periods of wakefulness
or light sleep, the REM rebound during the second half of the night is associated
with the completed alcohol metabolism and elimination from the body. The neurobiological
mechanisms responsible for the rebound of either wakefulness or REM sleep
are still unknown.

Some studies
also found an alcohol-related increase in the amount of SWS (i.e., stages
3 and 4 NREM sleep) in the first half of the sleep period (Williams and Salamy
1972). In addition to the alcohol dose consumed, the basal (i.e., normal)
level of SWS in the study population appeared to be the most likely factor
determining whether SWS was increased. For example, in a study of insomniacs
who had lower amounts of SWS than did healthy people when taking a placebo--a
typical finding in insomniacs--SWS increased when they consumed alcohol (Roehrs
et al. 1999). Conversely, alcohol did not affect SWS in a group of age-matched
healthy control subjects.

Another
population that typically shows lower levels of SWS compared with healthy
young adults are the elderly, but no studies have assessed alcohols
effects on the sleep of healthy elderly people. In sleep deprivation studies,
however, elderly participants show increases in SWS on the recovery night
after the sleep-deprivation period; possibly alcohol could similarly promote
SWS in elderly people. This finding does not imply, however, that alcohol
should be considered a potential sleep therapy in elderly people, because
tolerance to the SWS enhancement develops rapidly (Prinz et al. 1980).

Several
studies have assessed the effects of alcohol administration over several nights.
Such studies clearly demonstrated that tolerance to alcohols sedative
and sleep-stage effects develops within 3 nights (Williams and Salamy 1972)
and that the percentages of SWS and REM sleep return to basal levels after
that time. Furthermore, in some studies, the discontinuation of nightly alcohol
administration resulted in a REM sleep rebound--that is, an increase in REM
sleep beyond basal levels (Williams and Salamy 1972). However, not all studies
found such a rebound effect. This variability in results may be related to
several factors specific for each study, including the basal level of REM
sleep in the participants, the degree of alcohol-related REM suppression,
the extent of prior tolerance to REM suppression, and the dose and duration
of alcohol administration.

Alcohols
Effects on Hormone Function

The sleep-wake
cycle is organized in a circadian rhythm. To track this rhythm in humans,
researchers tend to use measurements of the core body temperature and of the
secretion of the hormone melatonin from the pineal gland in the brain, both
of which fluctuate in a typical pattern throughout the day. Accordingly, one
can also use these measurements to assess alcohols effects on the sleep-wake
cycle. As noted earlier, Kleitman (1939) first reported that alcohol administration
60 minutes before nocturnal bedtime altered body temperature compared with
placebo administration. Thus, alcohol administration initially resulted in
a reduction in core temperature, followed by a rebound increase in temperature.
Such a temperature-reducing (i.e., effect of alcohol also has been observed
in numerous other studies.

Various
hormones secreted by the pituitary gland in the brain also show circadian
variations, with secretory peaks occurring during the usual sleep period.
Some of these hormones are linked to sleep--if sleep is delayed, their secretory
peaks also are delayed. Conversely, the levels of other hormones peak at the
same time every night, even if sleep is delayed. One of the pituitary hormones
linked to sleep is growth hormone, whose secretion typically peaks with the
onset of SWS (Takahashi et al. 1969). In an early study, administration of
0.8 g/kg alcohol before bedtime suppressed growth-hormone secretion, despite
increasing the percentage of SWS (Prinz et al. 1980). A later study using
two different alcohol doses--0.5 and 1.0 g/kg--similarly found that alcohol
suppressed growth-hormone secretion at a dose-related rate (Ekman et al. 1996).
Thus, alcohol appears to affect growth-hormone secretion and SWS levels independently
(i.e., to dissociate growth hormone from SWS).

This hypothesis
is further supported by the results of repeated alcohol administration in
the first study (Prinz et al. 1980). In that study, the alcohol-related suppression
of growth-hormone secretion persisted over the 3 nights of alcohol administration,
whereas tolerance developed to the alcohol-related enhancement of SWS. The
clinical implications of alcohols inhibitory effects on growth hormone
and the dissociation of growth hormone and SWS are unclear, particularly with
chronic and excessive alcohol use. Unfortunately, these provocative findings
have not been pursued further.

Another
pituitary hormone linked to sleep is prolactin4 (4Together with other hormones,
prolactin regulates growth and development of the mammary glands and tinitiation
and maintenance of milk production in nursing women.); the
hormones secretion peaks 4 to 5 hours after sleep onset (Van Cauter
and Turek 1994). To date, researchers have not determined conclusively whether
alcohol affects prolactin release. In the study by Ekman and colleagues (1996),
alcohol did not affect prolactin levels. However, possibly even at the 1.0
g/kg alcohol dose, alcohol levels may no longer have been high enough 4 to
5 hours after sleep onset to affect prolactin secretion. Prinz and colleagues
(1980) did not measure prolactin levels in their study.

Alcohols
Effects on Neurochemicals

Alcohols
effects on central nervous system (CNS) function are mediated by its effects
on various brain chemicals (i.e., neurotransmitters and neuromodulators) that
are responsible for the transmission of nerve signals from one nerve cell
(i.e., neuron) to the next. These neurotransmitters
are released by the signal-emitting neuron and generally exert their actions
by interacting with certain molecules (i.e., receptors) located on the surface
of the signal-receiving neuron. Particularly at low doses, alcohol affects
CNS function primarily by interfering with the normal actions of the neurotransmitters
gammaaminobutyric acid (GABA) and glutamate, both of which also play critical
roles in wake-sleep states (Koob 1996).

GABA is
the major inhibitory neurotransmitter system in the CNS--that is, its interaction
with the signal-receiving neuron dampens the ability of that neuron to generate
a new nerve signal. Evidence from studies using various types of experimental
approaches has indicated that alcohol at low doses enhances GABAs actions
on the signal-receiving neuron, thereby reducing that neurons ability
to generate nerve signals even further (Mihic and Harris 1996). This observation
is significant, because many hypnotic drugs (i.e., barbiturates, benzodiazepines,
and the newer nonbenzodiazepine GABA agonists5) (5Agonists are substances that
mimic the actions of another molecule. For example, GABA agonists cause the
same reactions in other neurons as does GABA.) also act by facilitating
GABA function. Scientists have long considered GABA to play a major role in
sleep (Jones 2000). For example, GABA-releasing neurons are present in various
brain areas that are involved in the generation of SWS, such as the brainstem
reticular activation system, thalamus, hypothalamus, and basal forebrain.
Thus, facilitation of GABA-mediated inhibition is one possible explanation
for alcohols sedative and SWS-promoting effects.

Glutamate
is the major excitatory neurotransmitter in the CNS--that is, the interaction
of glutamate with its receptor activates the signal-receiving neuron to generate
a new nerve signal.Four types of glutamate receptors have been
identified, including the NMDA receptor (Tabakoff and Hoffman 1996). Anatomically,
glutamate-releasing neurons also are present in some of the brain areas that
promote SWS, such as the reticular activating system of the brainstem and
the forebrain (Jones 2000). NMDA agonists produce seizures; conversely, some
glutamate antagonists6 (6Antagonists are substances
that inhibit or interfere with the actions of another molecule. For example,
glutamate antagonists inhibit glutamates interactions with its receptors.)
are electrophysiological used as sedatives and anesthetics (Jones 2000).
Thus, glutamate is an important element in wakefulness and activation. Numerous
biochemical and studies have found that alcohol inhibits NMDA-receptor function,
thereby acting as a glutamate antagonist (e.g., Tabakoff and Hoffman 1996).
Consequently, alcohol inhibition of NMDA function may be another mechanism
through which alcohol derives its sedative effects.

In addition
to GABA and the glutamate-NMDA system, another agent that only recently has
been considered a candidate for mediating alcohols sleep effects is
adenosine. This molecule is not a neurotransmitter itself but modulates signal
transmission by other neurotransmitters, including GABA and glutamate. In
general, adenosine inhibits the function of glutamate in the CNS (Dunwiddie
1996). Alcohol appears to facilitate these inhibitory modulatory effects of
adenosine through several mechanisms, such as enhancing the formation of adenosine;
inhibiting the return of released adenosine into the cells, thereby prolonging
its actions; and enhancing adenosine-receptor function (Dunwiddie 1996). Adenosine
has been hypothesized to function as the sleep homeostat--the system that
monitors the accumulated amount of wakefulness and sleep and signals the need
for sleep (Bennington and Heller 1995). Its levels in the brain rise during
waking and decline during SWS. Thus, alcohol also may promote SWS and rapid
sleep onset by facilitating adenosine function.

The neurobiological
mechanism underlying alcohols suppression of REM sleep is unclear. One
neurotransmitter considered to play an important role in REM sleep is acetylcholine
(Bennington and Heller 1995). Like other neurotransmitters, this molecule
acts through several types of receptors, including nicotinic receptors and
muscarinic receptors. To date, only minimal evidence suggests a substantive
alcohol effect on acetylcholine. Furthermore, the evidence that does exist
indicates that alcohols effects occur through the nicotinic acetylcholine
receptor (Collins 1996); however, acetylcholine-mediated induction of REM
sleep occurs through muscarinic receptors (Bennington and Heller 1995). Thus,
it appears unlikely that the alcohol-related suppression of REM sleep is mediated
by alcohols effects on the acetylcholine system.

Glutamate
also is involved in the induction of some REM sleep phenomena (Bennington
and Heller 1995), and alcohols inhibition of glutamate was noted earlier
in this article (Tabakoff and Hoffman 1996). However, alcohol does not appear
to exert its sedative and REM-suppressive effects through the same mechanism
(e.g., glutamate inhibition), because both effects can be experimentally dissociated.
For example, in a recent report, caffeine reversed alcohols sedative
effects but not its REM suppressive effects7 (7Although unlikely at the low
dose used, caffeines own REM-suppressive effects may have been responsible
for the REM suppression observed.

As mentioned
earlier, the identification and recognition of sleep disorders have sensitized
clinical researchers to the importance of sleep quantity and continuity for
optimal daytime alertness and performance. In healthy people, even relatively
minimal (i.e., 1 to 3 hours) reductions in nocturnal sleep time for a single
night can reduce alertness and performance efficiency during the following
day. Moreover, these effects can accumulate across nights (Roehrs et al. 2000a).
Similarly, a disruption of sleep continuity by auditory stimuli, without reductions
in overall sleep time, results in reduced alertness and performance efficiency
in healthy people (Roehrs et al. 2000a). This fragmentation of sleep continuity is characterized
by increased amounts of stage 1 sleep and brief awakenings.

Several
studies have evaluated next-day performance and alertness in healthy people
who consumed alcohol before bedtime. In one study, young pilots drank alcohol
between 6 p.m. and 9 p.m. in quantities sufficient to result in blood alcohol
concentrations (BACs) of 0.10 and 0.12 percent right before bedtime. The following
morning, more than 14 hours after consuming alcohol and with BACs at 0, the
performance of pilots in a flight simulator was impaired relative to their
performance after consuming a placebo (Yesavage and Leirer 1986).

To investigate
whether alcohol-induced sleep disruption contributed to subsequent performance
impairment, Roehrs and colleagues (1991) administered alcohol to healthy people
before sleep, recorded their sleep, and assessed the participants alertness
and performance throughout the following day. The alcohol doses used resulted
in a BrAC of 0.06 percent before sleep. The study found that this dose was
associated with an increase in the amount of stage 1 sleep in the second half
of the night. The next day, the investigators assessed alertness using the
Multiple Sleep Latency Test (MSLT), a reliable and well-validated electrophysiological
test. Performance was evaluated with tests of auditory vigilance, in which
the participants had to respond to a certain sound, or divided attention tasks,
in which the participants had to perform two tasks simultaneously (Roehrs
et al. 2000a). The study found that in the alcohol-consuming
participants, next-day alertness as measured by the MSLT was reduced and divided-attention
performance was impaired (Roehrs et al. 1991), demonstrating that alcohol
can indirectly impair daytime alertness and performance through its disruptive
effects on sleep. These reductions in alertness and performance were relatively
minor in terms of percentage of the baseline values; in the performance of
difficult tasks (e.g., driving a car or flying an airplane), however, even
such minor impairments might have significant consequences.

Direct
Alcohol Effects on Daytime Alertness

Although
alcohol generally is classified as a depressant drug, in fact it has both
sedative and stimulatory effects. These differential (i.e., biphasic) effects
are dependent on the alcohol dose consumed and on the phase of the BAC (Pohorecky
1977). Thus, stimulatory effects are evident primarily at low-to moderate
alcohol doses and when BACs ascend to a peak. Conversely, alcohols sedative
effects occur at higher alcohol doses and when BACs decline. Nighttime sleep
studies that demonstrated alcohols sedative effects (i.e., reduced sleep
latencies) in healthy people typically used alcohol doses that resulted in
BrACs above 0.05 percent (Williams and Salamy 1972). Furthermore, the alcohol
generally was administered 30 to 60 minutes before sleep, thus allowing for
alcohol concentrations to peak before bedtime. In other studies that also
were conducted during the descending BAC phase, alcohol reduced sleep latency,
as measured by a standard MSLT, and impaired both attention and reaction-time
performance in a dose-dependent manner. These impairing effects persisted
for at least 2 hours after the alcohol had been completely metabolized as
evidenced by BrACs of 0 (Roehrs and Roth 1998).

Only one
daytime study using a modified MSLT assessed alcohols sleep effects
during both the ascending and descending phase of the BrACs. That study found
increased sleep latencies at peak BrACs relative to placebo, consistent with
alcohols stimulatory effects under these conditions (Papineau et al.
1988). During the subsequent descending phase of the BrACs, however, sleep
latencies were reduced relative to placebo, confirming alcohols biphasic
effects.

A series
of studies explored the modulation of alcohols daytime sedative and
performance-disrupting effects by a persons basal level of sleepiness
(Roehrs and Roth 1998). In these studies, the investigators first either shortened
or extended the participants scheduled nocturnal sleep time and then
administered alcohol doses of 0.4 to 0.8 g/kg the following day. Subsequently,
the researchers assessed the participants levels of sleepiness or alertness
as well as psychomotor performance for approximately 8 hours. The results
indicated that the level of sleepiness or alertness at the time of alcohol
administration altered alcohols subsequent sedating and performance-disrupting
effects. Thus, increased sleepiness compounded alcohols effects, whereas
increased alertness diminished alcohols effects.Furthermore, the investigators observed those
effects whether they compared sleepy versus alert healthy people, whether
they studied the same person before and after both sleep restriction and sleep
extension, or whether they studied the same person at various times of the
day when the levels of sleepiness are known to differ according to the typical
circadian rhythm.

Relationships
Between Nocturnal Sleep, Daytime Alertness, and Alcohol-Consumption History

Until
now, this article has explored alcohols effects on nocturnal sleep and
daytime alertness. The relationship between sleepiness-alertness and alcohol
consumption, however, may be bidirectional. Thus, some survey and laboratory
data suggest that variations in the duration of nocturnal sleep and level
of day-time sleepiness may play an important role in modulating alcohol consumption.
For example, a British survey found a negative correlation between sleep times
and alcohol consumption in men-- that is, shorter periods of sleep were associated
with heavier drinking (Palmer et al. 1980). Similarly, in a U.S. study of
young adults, participants who reported needing only 6 hours of sleep or less
had an earlier age of drinking onset and drank more per month than did participants
who needed more sleep (Schuckit and Bernstein 1981), leading the investigators
to hypothesize that short sleep is associated with heavier alcohol intake.

Laboratory
studies of alcohol and mood have identified some interesting relations between
daytime sleepiness-alertness and drinking. In such studies, the participants
preference for alcohol is studied by offering them several beverage choices
presented in color-coded cups in which the participants do not know which
of the cups contain an alcoholic beverage. After the participants have tasted
each beverage, they can choose which beverage they prefer. Using this procedure,
de Wit and colleagues (1987, 1989) found that moderate drinkers who preferred
an alcohol dose of 0.5 g/kg, which corresponds to approximately three drinks,
in the laboratory tests felt less alert at that time than did drinkers who
did not prefer alcohol. Furthermore, participants who preferred alcohol in
those studies generally experienced alcohol as increasing their elation and
vigor, whereas participants who did not prefer alcohol generally experienced
alcohol as increasing their sleepiness.

In an
alcohol challenge study, in which healthy young men received a certain alcohol
dose, the mens drinking histories predicted their subjective responses
to alcohol (Schuckit and Klein 1991). Those participants with histories of
greater alcohol consumption showed less self-rated sleepiness after the alcohol
challenge than did participants with histories of lower alcohol consumption.
Researchers do not know whether these individual differences in response to
alcohol reflect different physiological states (i.e., whether people are actually
more or less sleepy) or differences in the perception of a common physiological
state (i.e., whether all people experience the same physiological state but
differ in whether they perceive that state as being sleepy). In
the latter case, the different perceptions of alcohols effects may result
from differential expectations regarding alcohols effects.

Alcohols
Effects on the Sleep of Insomniacs

Approximately
10 to 15 percent of the U.S. general population experiences difficulties falling
asleep or maintaining sleep, or suffer from nonrestorative sleep (i.e., sleep
that does not result in a feeling of being rested) (Roehrs et al. 2000b). Moreover, 30 percent of people with persistent
insomnia in the general population have reported using alcohol to help them
sleep in the past year, and 67 percent of those people have reported that
alcohol was effective in inducing sleep (Ancoli-Israel and Roth 2000).

For several
reasons, studies conducted in healthy people sleeping at their usual bedtimes,
such as the studies reviewed in this article, do not adequately represent
the hypnotic potential of alcohol in people with insomnia. First, in healthy
people, sleep latency and sleep efficiency are already optimal, and further
improvement is difficult to demonstrate. Consequently, as previously noted,
alcohols effects on measures of sleep induction and maintenance in healthy
people are minimal and inconsistent. Second, the doses used in sleep studies
are generally much larger (i.e., resulting in BrACs greater than 0.05 percent,
which corresponds to more than three drinks) than the doses that insomniacs
typically report using (i.e., one to two drinks). Third, the same alcohol
dose may have different effects in healthy people and insomniacs. A recent
study compared the effects of an alcohol dose of 0.5 g/kg on the sleep of
insomniacs and age-matched healthy people (Roehrs et al. 1999). In the insomniacs,
but not in the healthy control subjects, this alcohol dose improved sleep
compared with a placebo. Further-more, the sleep disruption during the second
half of the night that occurs in healthy people after higher alcohol doses
was not observed in the insomniacs. Specifically, alcohol consumption in the
insomniacs increased their SWS to the levels of the age-matched control subjects.

During
a later phase of the same study (Roehrs et al. 1999), the participants also
had an opportunity to choose between beverages presented in color-coded cups
that contained various alcohol concentrations or a placebo. The participants
had previously experienced all of those beverages (i.e., they had taken them
one at a time before bedtime on different nights) and were asked to choose
the beverage that would best help them sleep. With this approach, the insomniacs
generally chose an alcohol-containing beverage, whereas the healthy people
chose the placebo-containing beverage. Furthermore, the average nightly alcohol
dose self-administered by the insomniacs was 0.45 g/kg (up to 0.6 g/kg was
possible), which is similar to the dose previously shown to improve the sleep
of the insomniacs and similar to the dose that insomniacs report using at
home.

The epidemiological
data and laboratory study findings indicating the preference for alcohol at
bedtime by insomniacs, compared with generate several questions. For example,
does this preference reflect the use of alcohol as self-medication for a sleep
problem, as a way to improve mood, or as a sleep medication that subsequently
becomes a mood-altering drug? And if alcohol use initially is,
or ultimately becomes, mood-altering behavior, what are the mood-altering
effects for the insomniac that reinforce alcohol consumption? Furthermore,
do insomniacs develop tolerance to alcohols sedative effects as do other
people? Do insomniacs increase their alcohol dose in successive nights? Does
hypnotic use at night generalize to daytime use? And ultimately, what are
the risks associated with the use of alcohol as a hypnotic? All these issues
have yet to be addressed. But these data again suggest that the alcohol-sleep
relation is interactive-- that is, disturbed nocturnal sleep increases the
likelihood of alcohol use, and alcohol has the potential to influence sleep.

Summary

Alcohol
has extensive effects on sleep and daytime sleepiness. In healthy people,
acute high alcohol doses disturb sleep, whereas in insomniacs, lower doses
may be beneficial. Data from healthy people suggest, however, that tolerance
to alcohols sedative effects probably develops rapidly. This tolerance
development may lead to excessive hypnotic use and, possibly, excessive daytime
use for insomniacs.

The effects
of alcohol appear to be bidirectional in that nocturnal sleep quantity and
continuity and subsequent levels of daytime sleepiness also influence alcohols
sedative and performance-impairing effects. Sleep quality and daytime sleepiness
may also relate to rates of alcohol drinking and become a gateway to excessive
alcohol use. To investigate these issues and identify the mechanisms underlying
the relationship between alcohol and sleep remain important tasks, as does
documenting alcohols effects on other physiological functions during
sleep.

References

ANCOLI-ISRAEL,
S., AND ROTH, T. Characteristics of insomnia in the United States: Results
of the 1991 National Sleep Foundation Survey. I. Sleep 22:S347-S353,
2000.

BENNINGTON,
J.H., AND HELLER, H.C. Restoration of brain energy metabolism as the function
of sleep. Progress in Neurobiology 45:347-365, 1995.

ALCOHOL
ALERT

At
What Blood Alcohol Level Is a Person Too Impaired To Drive Safely?

New
findings relevant to this and other questions can be found in Alcohol
Alert, the quarterly bulletin published by the National Institute
on Alcohol Abuse and Alcoholism. Alcohol Alert provides timely information on alcohol
research and treatment. Each issue addresses a specific topic in alcohol
research and summarizes critical findings in a brief, four-page, easy-to-read
format.

Alcohol
and Transportation Safety (No. 52)--discusses the effects
that even low blood alcohol concentration has on driving skills, and
reviews strategies designed to reduce alcohol-related crashes and repeat
drinking-and-driving offenses.